Clinical and angiographic correlates of leukocyte activation in unstable angina

Servi, Stefano De; Mazzone, Antonino; Ricevuti, Giovanni; Mazzucchelli, Iolanda; Fossati, Gianluca; Gritti, D.; L, Angoli; Specchia, Giuśeppe

doi:10.1016/0735-1097(95)00308-8

Cited by 64 publications

(51 citation statements)

References 21 publications

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“…This does not exclude local activation of T cells within the vulnerable arterial plaque, or it may imply that plaque rupture is not mediated by an Ag-driven Th1-type immune response. Although controversial, other investigators have also failed to find systemic signs of adaptive immune responses in patients with unstable angina despite evidence of inflammation and activation of innate immunity (17)(18)(19). Our findings substantiate the extensive experimental data on the role of the IFN-␥ axis in the pathogenesis of atherosclerosis.…”

Section: Discussionsupporting

confidence: 80%

An Inflammatory Pathway of IFN-γ Production in Coronary Atherosclerosis

Ranjbaran¹,

Sokol²,

Gallo³

et al. 2007

The Journal of Immunology

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Inflammation is associated with the pathogenesis of coronary atherosclerosis, although the mechanisms remain unclear. We investigated whether cytokine secretion by innate immune responses could contribute to the production of proarteriosclerotic Th1-type cytokines in human coronary atherosclerosis. Cytokines were measured by ELISA in the plasma of patients with coronary atherosclerosis undergoing cardiac catheterization. IL-18 was detected in all subjects, whereas a subset of patients demonstrated a coordinated induction of other IFN-γ-related cytokines. Specifically, elevated plasma levels of IL-12 correlated with that of IFN-γ and IFN-γ-inducible chemokines, defining an IFN-γ axis that was activated independently of IL-6 or C-reactive protein. Systemic inflammation triggered by cardiopulmonary bypass increased plasma levels of the IFN-γ axis, but not that of IL-18. Activation of the IFN-γ axis was not associated with acute coronary syndromes, but portended increased morbidity and mortality after 1-year follow-up. IL-12 and IL-18, but not other monokines, elicited secretion of IFN-γ and IFN-γ-inducible chemokines in human atherosclerotic coronary arteries maintained in organ culture. T cells were the principal source of IFN-γ in response to IL-12/IL-18 within the arterial wall. This inflammatory response did not require, but was synergistic with and primed for TCR signals. IL-12/IL-18-stimulated T cells displayed a cytokine-producing, nonproliferating, and noncytolytic phenotype, consistent with previous descriptions of lymphocytes in stable plaques. In contrast to cognate stimuli, IL-12/IL-18-dependent IFN-γ secretion was prevented by a p38 MAPK inhibitor and not by cyclosporine. In conclusion, circulating IL-12 may provide a mechanistic link between inflammation and Th1-type cytokine production in coronary atherosclerosis.

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Section: Discussionsupporting

confidence: 80%

An Inflammatory Pathway of IFN-γ Production in Coronary Atherosclerosis

Ranjbaran¹,

Sokol²,

Gallo³

et al. 2007

The Journal of Immunology

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“…Although 2 studies found evidence of T-cell activation in patients with unstable angina, 18,19 other studies reported negative results. 17,20 These contradictory findings may be explained in part by the differences in the inclusion criteria. However, immunologic response is a time-dependent phenomenon not easily assessed by an analysis limited to a single time point.…”

Section: Pasceri and Yeh A Tale Of Two Diseases 2125mentioning

confidence: 72%

“…The presence of systemic immune activation in unstable angina has been assessed by previous clinical studies [17][18][19][20] that…”

Section: Cd28mentioning

confidence: 99%

A Tale of Two Diseases

Pasceri¹,

Yeh

1999

Circulation

310

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A cute coronary syndromes are responsible for most of the morbidity and mortality caused by coronary atherosclerosis. Both unstable angina and acute myocardial infarction are characterized by coronary thrombosis, usually caused by rupture or fissuring of a coronary plaque. Yet the occurrence of plaque rupture and coronary thrombosis is not related to severity of coronary plaques, and functional factors other than the mere presence of atherosclerotic lesions play an important role.

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“…16 Increased expression of these markers on fasting leukocytes in patients with CVD and diabetes has also been described. 13,[17][18][19][20][21] Fasting leukocytes of patients with CVD have an increased lipid content when compared to controls, and it was suggested that this was attributable to the uptake of chylomicrons in the bloodstream. 22 Finally, leukocytes are able to internalize retinyl esters, as markers of intestinally derived TG-rich lipoproteins (TRLs).…”

mentioning

confidence: 99%

Leukocyte Activation by Triglyceride-Rich Lipoproteins

Alipour

Oostrom²,

Izraeljan³

et al. 2008

ATVB

190

152

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Objective-Postprandial lipemia has been linked to atherosclerosis and inflammation. Because leukocyte activation is obligatory for atherogenesis, leukocyte activation by triglyceride-rich lipoproteins (TRLs) was investigated. Methods and Results-The expression of CD11b and CD66b after incubation with glucose and native and artificial TRLs (NTRL and ATRL) in vivo and in vitro was evaluated by flowcytometry. Oral fat loading tests showed an increased expression of CD11b on monocytes and neutrophils and CD66b on neutrophils. In 11 volunteers, postprandial leukocytes became enriched with meal-derived fatty acids ([1-13 C]16:0) suggesting uptake of exogenous fat. ApoB binding on leukocytes measured by flowcytometry in 65 subjects was highest on neutrophils and monocytes suggesting adherence of apoB-containing lipoproteins. Physiological concentrations of TRLs showed 62% increased neutrophil CD11b and a dose-dependent increased monocyte CD11b up to 84% in vitro. Incubations with lipid emulsions in the hypertriglyceridemic range showed a 5-fold increased monocyte CD11b expression, which was higher than the positive control (fMLP), and a dose-dependent 2-to 3-fold increased neutrophil CD11b and CD66b. The oxidative scavenger DMTU decreased the neutrophil CD66b expression by 36%. Conclusion-Acute hypertriglyceridemia is a leukocyte activator most likely by direct interaction between TRLs and leukocytes and uptake of fatty acids. TG-mediated leukocyte activation is an alternative proinflammatory and proatherogenic mechanism of hypertriglyceridemia in part associated to the generation of oxidative stress.

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Clinical and angiographic correlates of leukocyte activation in unstable angina

Cited by 64 publications

References 21 publications

An Inflammatory Pathway of IFN-γ Production in Coronary Atherosclerosis

An Inflammatory Pathway of IFN-γ Production in Coronary Atherosclerosis

A Tale of Two Diseases

Leukocyte Activation by Triglyceride-Rich Lipoproteins

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